The broad categories which are included in the project are: 1) Characterizing functionally the mechanism by which various substrates cross the plasma membrane of different mammalian cells; 2) identifying the metabolic and humoral factors which influence the transport of various substrates across the plasma membrane; 3) developing techniques which will distinguish between binding of a substrate to the membrane and translocation of the substrate across the membrane; 4) characterizing the mechanism by which the membrane transport of various substrates is altered in certain disease; and 5) relating these alterations of membrane transport to the pathogenesis and clinical manifestations of the disease.